In this renewal proposal we set forth our plans to undertake the stereospecific total synthesis of potent tumor-inhibitory substances having highly oxidized rings. These include crotepoxide, senepoxide, pipoxide, triptolide, tripdiolide and stemolide. We also plan to pursue the synthesis of the structurally related pharmacologically active fungal metabolite LLZ-1220. Much of our proposed work involves the application of stereospecific transformations of arene oxides which we have been developing. Such reactive substances may also be true biosynthetic intermediates in many cases. For this reason we wish to perform some plant feeding experiments aimed at elucidating biogenetic pathways to some of these compounds. Our long-range plans include the preparation of a number of structural analogs to test our ideas on the mechanisms responsible for tumor-inhibitory activity.